Bone repair is a subject of intensive investigation in human health care. Current therapy in bone reconstructive surgery frequently uses autograft or allograft although restrictions on these bone transplants exist. These restrictions include donor site morbidity and donor shortage for autograft (Pross R, editor. Orthop Knowledge Update 1990;3; Damien J C et al J Appl Biomater 1991;2:187-208.) and immunologic response and risk of transmitting diseases for allograft (Pross R, editor. Orthop Knowledge Update 1990:3; Binderman I et al, CRC Handbook of Bioactive Ceramics. Boca Raton, Fla.: CRC Press; 1990. p45-51). Heretofore, numerous bone substitutes using metals, ceramics, and polymers have been developed. However, each has specific disadvantages, and none of them can take the places of autograft and allograft in current clinical practice. One important reason for the priority of autograft and allograft is that their composition and microstructure are the same as the bone to be repaired therefore possess biological advantages. Under the principles of tissue engineering, a material, which has similar composition and microstructure with natural bone, is expected to be a promising biological substitute for regenerating, replacing, or enhancing tissue function.
It has been known that natural bone is a complex biomineralized system with an intricate hierarchial structure. Collagen and calcium phosphate minerals are the main substances existed in bone. The calcium phosphate minerals in bone exist as irregularly shaped mineral platelets, whose crystallographic c-axes are oriented generally parallel to one another. The crystal width varies (30-45 nm) but crystal thickness is uniform (˜4-6 nm). Adjacent platelets are spatially separated by a layer of collagen whose thickness is 4.2±1.0 nm in minimum (W. J. Landis et al, J Structure Biology 110,39-54(1993)). The finely aligned collagen, which exists as a most important extracellular matrix, is a key factor influencing cell activities.
Except the composition and microstructure of natural bone the interconnecting porous structure of natural bone also play an important role in nutrient transportation and ingrowth of new bone.
In order to take the roles played by autograft and allograft, bone substitute materials made under the principle of biomimetic strategy, and which mimic the natural bone both in composition and microstructure, are still in great demand.
Thus, one of the objects of this invention is to provide a nano-calcium phosphates/collagen composite that mimics the natural bone, both in composition and microstructure so as to be used in the manufacture of bone substitute materials.
Another object of this invention is to provide porous bone substitute and tissue engineering scaffolds having excellent biocompatibility and biodegradability, which promote bone repair and regeneration. Said porous scaffolds are made by a complex of the nano-calcium phosphates/collagen composite and poly(lactic acid) or poly(lactic acid-co-glycolic acid).